ABSTRACT There is growing evidence linking cancers and other diseases to the dysregulation of arginine deimination, or citrullination. This small post-translational modification (PTM) abates the charge on the arginine sidechain changing the local chemical environment. I hypothesize that citrullination patterns are variant among cell types, including cancerous and inflamed tissue lines, and therefore represent specific biomarkers. On that account, the long-term goal of this proposal is to determine specific citrullinated arginine residues in order to make inferences on the role this PTM plays on various forms of breast cancer tissue and, consequently, to uncover unambiguous biomarkers for novel diagnostics. To explore this, I have synthesized various chemical probes which will select for citrulline residues. These probes are unique in that they can then be used to enrich, visualize, and quantify citrulline-containing peptides. Concerning the identity of specific sites of citrullination, this probe will be used in conjunction with tandem mass spectrometry. Proteomic samples will be prepared using tissue samples supplied by my collaborators as well as the University of Massachusetts Medical School Tissue and Tumor Bank. From here, I will begin to compile a directory of markers associated with various cancers, autoimmune, and inflammatory diseases.